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Type 2 diabetes linked to renal cell carcinoma risk in women
Type 2 diabetes is associated with an increased risk for renal cell carcinoma in women, independent of other risk factors, such as obesity and hypertension, according to findings published in Diabetes Care.
A recent meta-analysis of 11 cohort and seven case-control studies found a modest association between diabetes and kidney cancer, Alejandro Sanchez, MD, a surgeon in the department of urology at Massachusetts General Hospital in Boston, and colleagues wrote in the study background. However, only five of the included studies were adjusted for obesity status, whereas two studies were adjusted for hypertension status.
“Because hypertension and obesity are established risk factors for [renal cell carcinoma] and are also strongly linked with type 2 diabetes, accounting for these conditions in evaluating the association of type 2 diabetes and [renal cell carcinoma] is crucial,” Sanchez and colleagues wrote. “However, few studies evaluating this relationship have adjusted for these important confounders.”
The researchers analyzed data from 117,570 women participating in the Nurses’ Health Study (NHS), followed from 1976, and 48,866 men participating in the Health Professionals Follow-up Study (HPFS), followed from 1986. Participants self-reported diabetes and renal cell carcinoma status every 2 years via questionnaires; deaths were identified by reports from family members and the National Death Index. Researchers treated type 2 diabetes status as a time-dependent exposure, calculating person-time before and after diabetes diagnosis. Person-time was also calculated from return-date of the baseline questionnaire until first renal cell carcinoma diagnosis, death from any cause or end of follow-up (June 2014 for the NHS and January 2014 for the HPFS). Researchers used Cox proportional hazard models stratified by age and calendar time to evaluate the relationship between type 2 diabetes and total and fatal renal cell carcinoma.
During 38 years of follow-up for the NHS, researchers observed 418 incident renal cell carcinoma cases, including 120 fatal cases. For the HPFS, researchers observed 302 incident cases of renal cell carcinoma during 28 years of follow-up, including 87 fatal cases.
In analyses for both cohorts, researchers found that women with type 2 diabetes had a greater risk for developing renal cell carcinoma (HR = 1.53; 95% CI, 1.14-2.04), whereas men did not (HR = 0.89; 95% CI, 0.56-1.41). There was no link observed between type 2 diabetes status and fatal renal cell carcinoma for women or men, according to researchers.
In sensitivity analyses, excluding renal cell carcinoma cases diagnosed within the first 2 years after a type 2 diabetes diagnosis attenuated the association between type 2 diabetes and renal cell carcinoma for women in the NHS (HR = 1.29; 95% CI, 0.94-1.76) and did not materially change the results for men.
In analyzing renal cell carcinoma by histologic subtype, researchers noted a stronger association for type 2 diabetes and risk for non-clear cell renal cell carcinoma (HR = 2.68; 95% CI, 1.32-5.44) vs. clear cell renal cell carcinoma (HR = 1.35; 95% CI, 0.94-1.93). Additionally, when stratifying by diabetes duration, risk for renal cell carcinoma persisted for women with a diabetes duration of 5 years or less (HR = 2.15; 95% CI, 1.44-3.23), but not for women with a diabetes duration of more than 5 years (HR = 1.22; 95% CI, 0.84-1.78).
“It is possible that the association between diabetes and [renal cell carcinoma] is due to detection bias, particularly given the attenuated association when we excluded [renal cell carcinoma] cases diagnosed within the first 2 years after a type 2 diabetes diagnosis,” the researchers wrote. “There is evidence that a diagnosis of type 2 diabetes increases the chance of diagnosis of multiple cancer types owing to increased medical scrutiny. Alternatively, increased risk of [renal cell carcinoma] sooner after type 2 diabetes may be related to hyperinsulemia that occurs early in the course of type 2 diabetes.” – by Regina Schaffer
Disclosures: The authors report no relevant financial disclosures.